System and method for electrical stimulation of salivation

ABSTRACT

A system, a device and a method for electrically detecting a lack of saliva in an oral cavity of an individual and for electrically stimulating the oral cavity so as to induce production of saliva from at least one salivary gland are disclosed. The system includes a control device for detecting a measure of salivation in the individual and for delivering electrical impulses to the oral cavity of the individual, a check device for checking a state of the control device and for modifying at least one parameter of the control device, and, a computer device for exchanging information with the check device.

REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority of PCT applicationPCT/IL02/00085 filed Jan. 30, 2002, which in turn claims the benefit ofpriority to U.S. provisional application No. 60/264,686 filed Jan. 302001.

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to a system and method for electricalstimulation of salivation and, more particularly, to a system and amethod of using same for electrically detecting a lack of saliva in theoral cavity and for electrically stimulating the oral cavity so as toinduce the production of saliva from the salivary glands.

Saliva performs many critical functions in the oral cavity and isessential for the maintenance of oral health. The accomplishment of thefunctions of saliva depends on proper salivary production. Salivaneutralizes acid that promotes dental caries and aids in theremineralization of areas of incipient caries development. Salivacontains specific antifungal agents and reduces bacteria in the oralcavity by a number of means including dilution, aggregating factors, andmicrobicidal enzymes. Salivary glycoproteins reduce intraoral trauma(between different oral structures such as teeth, cheek, tongue andlips) by lubricating the hard and soft tissues and saliva aidsswallowing by facilitating bolus formation. Salivary enzymes such aslipase and amylase start the digestion of food. Taste perception isfacilitated by salivary dilution and delivery of food particles to thetaste buds.

Saliva is produced by the salivary glands. Each individual has threepairs of salivary glands: the parotid glands (the largest, which lieunder the skin of the cheeks), and the submandibular and the sublingual,which are located at the floor of the mouth. The secretion of saliva isregulated by the autonomic nervous system.

Xerostomia, or dry mouth, is a very common complaint. While between20-30% of the adult population may complain of it at some time, for 1-2%of the population it is a serious problem. The chronic lack of saliva isassociated with rampant, severe dental caries, difficulty chewing,painful swallowing, diminished taste and smell, and oral fungalinfections.

Xerostomia can result from many different causes. The most prevalent isas a side effect of one or more medications that inhibit salivationthrough anticholinergic or other mechanisms. Hundreds of drugs are knownto have this side effect, especially antidepressants, MAO inhibitors,neuroleptics, parasympatholytics, some analgesics and certaincombinations of anti-hypertensive agents. A variety of autoimmunedisorders, particularly, Sjogren's syndrome, are another importantcause. One to three million Americans suffer from Sjogren's syndrome.Severe salivary gland hypofunction also results from therapeuticirradiation of the head and neck as well as other causes including otherdiseases such as sarcoidosis, amyloidosis, graft-versus-host disease,HIV infection, diabetes, Alzheimer disease, depression, dysautonomia andFabry disease. Aging itself appears to be a cause of xerostomia as well.

Treatment of xerostomia is difficult and while there are some currentlyavailable treatments, they are not satisfactory. Symptomatic treatmentsinclude sialogogues such as sugarless hard candies or chewing gum.Symptomatic palliative relief can sometimes be obtained by frequent sipsof water or use of a saliva substitute. In patients whose xerostomia hasa non-pharmacologic cause, oral pilocarpine (if not contraindicated) maybe helpful but has the side effects of perspiration, flushing, urinaryurgency and lacrimation.

It is well known that it is possible to increase salivation bystimulation of the salivary glands by low power electric current.Studies have demonstrated that the salivary glands respond to discretestimulatory pulses with increased salivation (Weiss et al J OralMaxillo-facial Surg 44:845-50, 1996; Steller et al J Dental Res 67:1334-7, 1988; Talal et al Rheum Int 12:43-5, 1992)

U.S. Pat. Nos. 4,519,400 and 4,637,405 to Brenman et al teach a deviceand method for electrical induction of salivation. The device includes ahousing which may be received in the oral cavity of a user, the housingenclosing electronic signal generating means and electrodes for applyinga signal to neurally sensitive locations of the oral cavity to inducesalivation. The device can be held in the oral cavity of the user for aperiod of time and be removed therefrom and to be reinserted later, orit can be fixed to the palate by clips fitted around molar teeth of theupper jaw. In its method aspect the invention involves stimulation ofsalivation by the application of an electrical signal to neurallysensitive locations

EP 278847 relates to an apparatus for stimulating the secretion ofsaliva and has the form of a pellet made of a non-conductive materialwith electrodes on opposite faces thereof. The apparatus has no means offirm attachment within the mouth and is only held freely within themouth and is moved from one place to another by aid of the tongue. Inaddition, as with the devices of Brenman et al, none of these devicescan be operated by either remote or feedback control.

WO 00/44439 teaches a device and method for inducing salivation using animplanted device. Several generations of the device of the invention areenvisaged including those with controllable or changeable electricalparameters, and those where changing the parameters is under the controlof a salivation sensor which constantly senses mouth humidity and formsa feedback loop with the device. The invention does not however disclosehow such control can be accomplished and is not enabling as to how sucha salivation sensor might operate and how feedback control can beeffected.

There is thus a widely recognized need for, and it would be highlyadvantageous to have, a system and method for electrical stimulation ofsalivation devoid of the above limitation.

SUMMARY OF THE INVENTION

According to one aspect of the present invention there is provided asystem for electrically detecting a lack of saliva in an oral cavity ofan individual and for electrically stimulating the oral cavity so as toinduce production of saliva from at least one salivary gland, the systemincluding: (a) a control device for detecting a measure of salivation inthe individual and for delivering electrical impulses to the oral cavityof the individual, (b) a check device for checking a state of thecontrol device and for modifying at least one parameter of the controldevice, and, (c) a computer device for exchanging information with thecheck device.

According to another aspect of the present invention there is provided adevice for electrically detecting a measure of saliva in an oral cavityof an individual and for delivering electrical impulses to the oralcavity of the individual so as to induce production of saliva from atleast one salivary gland, the device, also known as the control device,including: (a) a hermetically sealed housing adapted to be fixablewithin the oral cavity, (b) an electrical utility enclosed within thehousing for detecting an input signal for detection of the measure ofsalivation and for generating the electrical impulses, the electricalutility including a power source and a signal generator, and (c) atleast one pair of electrodes electrically coupled to the electricalutility, the at least one pair of electrodes adapted for contact with atissue of the oral cavity.

According to yet another aspect of the present invention there isprovided a method for electrical stimulation of salivation including thesteps of: (a) attaching a device for electrically detecting a measure ofsaliva in an oral cavity of an individual and for delivering electricalimpulses to the oral cavity of the individual so as to induce productionof saliva from at least one salivary gland, the device having at leastone pair of electrodes, the electrodes being placed against a tissue ofthe oral cavity, (b) detecting an input signal indicative of the measureof moisture within the oral cavity, (c) comparing the measure to amoisture limit value, and (d) delivering the electrical impulses basedon a result of the comparing.

According to still another aspect of the present invention, there isprovided a housing for an intraoral device, the intraoral device beingconfigured so as to be fixable to at least one tooth within an oralcavity of an individual, the housing including: (a) a body and (b) anattachment element for fixing the body to the at least one tooth,wherein, the attachment element includes at least one clasp forattaching the body to the at least one tooth, the at least one claspincluding at least one elastic jaw, whereby the at least one clasp fixesonto the at least one tooth by the pressure of the at least one jawagainst the at least one tooth.

According to further features in preferred embodiments of the inventiondescribed below, the control device of the system includes: (1) ahermetically sealed housing adapted to be fixable within the oralcavity, (2) an electrical utility enclosed within the housing fordetecting an input signal for detection of the measure of salivation andfor generating the electrical impulses, the electrical utility includinga power source and a signal generator, and (3) at least one pair ofelectrodes electrically coupled to the electrical utility, the at leastone pair of electrodes adapted for contact with a tissue of the oralcavity.

According to still further features in the described preferredembodiments the power source is a battery.

According to still further features in the described preferredembodiments the battery is rechargeable, and the electrical utilityincludes a charge battery block for charging the battery.

According to still further features in the described preferredembodiments the electrical utility further includes a microprocessor forcontrolling at least one parameter of the signal generator.

According to still further features in the described preferredembodiments the microprocessor includes a memory device for storinginformation about the at least one parameter.

According to still further features in the described preferredembodiments the memory device is configured for storing a set ofoperating rules.

According to still further features in the described preferredembodiments the memory device stores a predefined and preinstalled setof the operating rules.

According to still further features in the described preferredembodiments the at least one pair of electrodes are adapted to be usedfor more than one function.

According to still further features in the described preferredembodiments the more than one function is selected from the groupconsisting of emitting the electrical impulses, receiving the inputsignal, exchanging information between the control device and the checkdevice, and recharging the power supply.

According to still further features in the described preferredembodiments the housing includes an electrically conductive exteriorportion, the electrically conductive portion serving as a component ofthe at least one pair of electrodes.

According to still further features in the described preferredembodiments the housing is adapted to be implanted within the tissue ofthe oral cavity.

According to still further features in the described preferredembodiments the housing includes an attachment element adapted to attachthe housing to at least one tooth.

According to still further features in the described preferredembodiments the attachment element is adapted so that the housing iscapable of being repeatedly attached and removed by the individual.

According to still further features in the described preferredembodiments the at least one tooth is a mandibular tooth.

According to still further features in the described preferredembodiments the at least one tooth is selected from the group consistingof a premolar tooth and a molar tooth.

According to still further features in the described preferredembodiments the attachment element is a mouth guard.

According to still further features in the described preferredembodiments the attachment element includes at least one clasp forattaching the control device to the at least one tooth, the at least oneclasp including at least one elastic jaw, whereby the at least one claspfixes onto the at least one tooth by the pressure of the at least onejaw against the at least one tooth.

According to still further features in the described preferredembodiments at least one jaw has a face, the face having an adhesionmodification for increasing fixation of the at least one jaw to the atleast one tooth.

According to still further features in the described preferredembodiments the face has a surface area and said adhesion modificationincreases the surface area of said face.

According to still further features in the described preferredembodiments the adhesion modification includes at least one groove onthe face.

According to still further features in the described preferredembodiments the signal generator includes a mechanism for producing theimpulses and the impulses are square-waved shaped.

According to still further features in the described preferredembodiments the signal generator includes a mechanism for producing aseries of the impulses, the impulses having an intensity of between 10and 200 microamperes, and each of the pulses lasting from 5 to 100milliseconds.

According to still further features in the described preferredembodiments the control device is fixed in the oral cavity so as topreferably stimulate the submandibular and sublingual salivary glands.

According to still further features in the described preferredembodiments the measure of salivation is a relaxation time, therelaxation time being a measure of time required for a voltagedifference between the at least one pair of electrodes to reach apredetermined level of an initial value of the voltage difference aftera measuring pulse is applied.

According to still further features in the described preferredembodiments the predetermined level is selected from the groupconsisting of 40% and 50%.

According to still further features in the described preferredembodiments steps (b) through (d) of the method for electricalstimulation of salivation are repeated iteratively.

According to still further features in the described preferredembodiments the method further includes the step of modifying aparameter of the device.

The present invention successfully addresses the shortcomings of thepresently known configurations by providing a system and method forelectrical stimulation of salivation that can be used for the treatmentof xerostomia that can be used to electrically detect a lack of salivain the oral cavity and for electrically stimulating the oral cavity soas to induce the production of saliva from the salivary glands. Theprincipal advantage of the present invention over the prior art is thatthe system according to the present invention is constructed anddesigned so that the system can electrically detect a lack of saliva,the parameters of the electrical stimulation can be controlled, and theparameters can be controlled under feedback control using the electricaldetection of saliva quantity.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings. With specific reference now tothe drawings in detail, it is stressed that the particulars shown are byway of example and for purposes of illustrative discussion of thepreferred embodiments of the present invention only, and are presentedin the cause of providing what is believed to be the most useful andreadily understood description of the principles and conceptual aspectsof the invention. In this regard, no attempt is made to show structuraldetails of the invention in more detail than is necessary for afundamental understanding of the invention, the description taken withthe drawings making apparent to those skilled in the art how the severalforms of the invention may be embodied in practice.

In the drawings:

FIG. 1 is a schematic diagram of a physical model of the salivaryglands;

FIG. 2 is a graph of measured electrical activity returned after astimulatory pulse is applied to the circuit of FIG. 1;

FIG. 3 is a functional block diagram of a preferred embodiment of thesystem for electrical stimulation of salivation of the presentinvention;

FIG. 4 is a functional block diagram showing the major components andconnections of a control device of the system according to the presentinvention;

FIG. 5 is a functional block diagram showing the major components andconnections of a check device of the system according to the presentinvention;

FIG. 6A shows the control device of the system according to the presentinvention attached to a tooth;

FIG. 6B shows the control device of the system according to the presentinvention attached to the mandibular teeth by a mouth guard;

FIG. 7 is an illustrative flowchart for the purpose of understanding themethod according to the present invention;

FIG. 8 is an illustrative flowchart in greater detail for the purpose ofunderstanding the method according to the present invention;

FIG. 9A is a graph illustrating the results of experimental studies onthe relationship of relaxation time and saliva quantity;

FIG. 9B is a graph illustrating the results of repeated detailedexperimental studies on the relationship of relaxation time and salivaquantity in one subject;

FIG. 10A is a side view illustrating a preferred embodiment of thehousing of the control device of the system according to the presentinvention;

FIG. 10B is a perspective view illustrating a preferred embodiment ofthe housing of the control device of the system according to the presentinvention;

FIG. 11 is a schematic circuit diagram illustrating aspects of thecircuitry according to the present invention; and,

FIGS. 12-14 illustrate alternate examples of methods of operation of thepresent invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is of a system and method for electricalstimulation of salivation that can be used for the treatment ofxerostomia. Specifically, the present invention can be used toelectrically detect a lack of saliva in the oral cavity and forelectrically stimulating the oral cavity so as to induce the productionof saliva from the salivary glands. The principal advantage of thepresent invention over the prior art is that the system according to thepresent invention is constructed and designed so that the system canelectrically detect a lack of saliva, the parameters of the electricalstimulation can be controlled, and the parameters can be controlledunder feedback control using the electrical detection of salivaquantity.

The principles and operation of a system and method for electricalstimulation of salivation according to the present invention may bebetter understood with reference to the drawings and accompanyingdescriptions.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not limited in its applicationto the details of construction and the arrangement of the components setforth in the following description or illustrated in the drawings. Theinvention is capable of other embodiments or of being practiced orcarried out in various ways. Also, it is to be understood that thephraseology and terminology employed herein is for the purpose ofdescription and should not be regarded as limiting.

Referring now to the drawings, FIG. 1 is a schematic diagram of aphysical model of the salivary glands. According this model, thesalivary glands can be described as an electrical circuit (10) with aninput resistor R1 (12) connected to a parallel resistor R2 (14) andcapacitor C (16). When a current pulse is applied to circuit 10, acurrent reply is returned. The resulting reply is measured and defines acurve (18) as illustrated in FIG. 2. From curve 18, various parametersare estimated including resistance, capacity and the time for thecircuit to discharge the circuit's capacity following the pulse. Thedischarge time is the time required by the circuit to return to itsbaseline activity after receiving a stimulation pulse.

For purposes of this specification and the accompanying claims, the term“relaxation time” [20] refers to, and is defined as, the time (28)required for a measured voltage difference (22) to reach a predeterminedlevel, preferably 40% (26), or 50% in some embodiments, of its initialvalue (24), after a measuring pulse (17) is applied.

Based on this model, as further described hereinbelow in greater detail,an electrical pulse is administered to the salivary glands and thenfollowing a short pause (several seconds) the voltage difference betweenthe two electrodes is measured. These measurements are used to determinethe relaxation time 20 of the gland. Results of experimentalinvestigation, detailed herein below under “Examples”, have demonstrateda good correlation between the relaxation time 20 of the gland andglandular activity, the glandular activity being defined as the quantityof saliva present.

FIG. 3 shows a functional block diagram of a preferred embodiment of thesystem for electrical stimulation of salivation of the presentinvention, the system generally designated 30. As illustrated in FIG. 3,system 30 comprises 3 parts: a control device 32, a check device 34 anda computer device 36. Control device 32 functions to emit pulses to atleast one salivary gland in the mouth of an individual. Check device 34functions to check the state of control device 32, to install, change,modify and delete the stimulation pulse parameters of control device 32and to exchange information with computer device 36. The exchange ofinformation between check device 34 and computer device 36 includestransmission of data from control device 32 to computer device 36 andreception of stimulation pulse parameters from computer device 36 to betransferred to control device 32. This configuration of system 30 givesto the doctor who is the operator of system 30 the full picture aboutthe treatment of the patient, including the possibility of analyzing thestate of the patient (e.g., relaxation time, parameters of treatment,correlation of relaxation time with the pulse parameters) and changingthe stimulation pulse parameters, including quantity and timeparameters.

FIG. 4 illustrates the components of control device 32 in greaterdetail. Control device 32 has a hermetically sealed housing 38 encasingan electric utility generally designated 40. In certain preferredembodiments of the present invention, housing 38 is adapted to beattached to at least one tooth and in other preferred embodimentshousing 38 is adapted to be permanently implanted within tissues of theoral cavity. Electric utility 40 comprises a battery 42 and anelectronic circuitry 44. Battery 42 is preferably a miniature batterysupplying low voltage (preferably between 3-5 volts, most preferably 3volts) and can be of a perishable type or can be of a rechargeable type.Electronic circuitry 44 preferably includes the following components: aconverter 46, a timer 48, a current reference 50, a charge battery block52, a first input-output multiplexer 54, a measuring multiplexer 56, ananalog-digital converter 58, and a first microcontroller 60, withoperative associations, signal flow, and electrical couplings asindicated in FIG. 4. First microcontroller 60 is further divided intosubunit blocks as illustrated in FIG. 4 including: a first control block62, a first calculation block 64, a first data memory 66, a first set-upparameters block 68 and a first pattern definition block 70. First datamemory 66 includes a writeable memory device such as, but not limitedto, ROM, RAM, PROM, EPROM, EEPROM, flash memory etc. Blocks 62, 64, 68,and 70 are each program modules, performing the respective processorfunctions described in their titles. First input-output multiplexer 54is operatively associated with and electrically connected to at leastone pair of electrodes 72. At times housing 38 may be provided with anelectrically conducting exterior covering the whole or part of thesurface of housing 38, in which case the electrically conducting portionof the housing may serve as one of the electrodes 72 of device 32. Whenhousing 38 serves as one of the electrodes 72 it is insulated.Preferably device 32 contains only one pair of bi-directional,multi-functional electrodes 72. This one pair of bi-directional,multi-functional electrodes 72 functions to emit stimulatory pulses,receive returning electrical signals, receive current for chargingbattery 42, and for communication with check device 34 to exchangeinformation between control device 32 and check device 34. Alternativelydevice 32 may be provided with independent electrode pair assemblies forseparate functions or alternatively one electrode may be shared by morethan one functional component and the other electrode may be separatefor each functional component. Electrodes 72 are preferably insulatedfrom housing 38 and have exposed conducting ends. The exposed conductingends are placed in the vicinity of either a nerve innervating a salivarygland or in the vicinity of a gland itself as is further describedhereinbelow.

All the functional blocks may either be individual microprocessors orother CPU's or control programs for a multiple-use processor. They mayinclude a factory-set group of default rules.

Converter 46 converts low voltage supplied from battery 42 to highvoltage for supplying current reference 50, from 3v to 6v, as anon-limiting example. Timer 48 provides time pulses to firstmicrocontroller 60. Current reference 50 serves as a signal generator tosupply stimulation pulses of electrical current with parameters underthe control of first microcontroller 60. Charge battery block 52 ispresent only in those preferred embodiments that contain a rechargeablebattery as battery 42 and is used to apply a charge to rechargeablebattery 42. First input-output multiplexer 54, is connected to currentreference 50, charge battery block 52, first microcontroller 60, andmeasuring multiplexer 56 with operative associations and signal flow asindicated in FIG. 4, as well as to the at least one pair of electrodes72. First input-output multiplexer 54 performs the following functions:emit stimulatory pulses via electrodes 72 to salivary gland, measureelectrical activity state of salivary gland, charge battery, (in whichcase multiplexer 54 receives current and transfers the current to chargebattery block 52), transmit information to check device 34 and receiveinformation from check device 34. Measuring multiplexer 56 can switchbetween measuring the voltage output of the battery, for checkingbattery condition (and determining whether battery needs to be chargedor changed), and measuring electrode voltage for determining theelectrode contact quality and for determining relaxation time.Analog-digital converter 58 converts analog information into digitalcode for processing by first microcontroller 60. First microcontroller60 performs all of the calculation and data processing functions ofdevice 32 as described herein. Additional components such as, but notlimited to, contacts and wires, may be required to establish theconnections as described hereinabove. One of ordinary skills in the artwould know how to operatively assemble these components.

FIG. 11 is an a schematic circuit diagram illustrating a non-limitingexample of a preferred embodiment of a circuit corresponding to featuresof control device 32 as illustrated in the block diagram, FIG. 4. Such acircuit as illustrated (as a non-limiting example) in FIG. 11 is capableof being fabricated as a two level circuit, 0.2 mm thick and 16 mm indiameter, using SMD packing, with a 3V lithium battery (e.g. 42) mountedon top, capable of being placed in housing (e.g. 38) of appropriate sizefor fixation in the oral cavity.

The components and connections of check device 34 are illustrated ingreater detail in FIG. 5. check device 34 preferably includes a secondinput-output multiplexer 74, a comparator 76, a keyboard 78, a display80, a PC block connection 82, a second microcontroller 84, a chargebattery supply 90, and a power supply 91. The operative associations,signal flow, and electrical couplings between the components of checkdevice 34 are preferably as indicated in FIG. 5. Second input-outputmultiplexer 74 is operatively associated with at least one pair ofinput-output connections 86 which serve to facilitate communicationbetween check device 34 and control device 32. Second input-outputmultiplexer 74 performs the following functions: transmits informationto control device 32, receives information from control device 32 andcharges battery 42. Comparator 76 checks the signal from control device32. Information to be installed in system 30 may be introduced (input)into check device 34 via keyboard 78 as is known in the art. Data isvisually presented to the operator by display 80. Non-limiting examplesof display 80 are conventional computer monitors, cathode ray tubedisplay screens, liquid crystal displays and light emitting diodes. PCblock connection 82 executes the communication between check device 34and computer device 36 via at least one communication channel 88.Communication channel 88 utilizes any means of data transfer including,but not limited to, data transfer by a direct cable, connection, atelephone connection, a cellular phone connection, an Internetconnection, an infrared frequency connection, a local area networkconnection, and a radio frequency connection. Also specificallyenvisaged as being encompassed by communication channel 88 is datatransfer through transfer of tangible media containing data betweendevices 34 and 36. Such tangible media includes, but is not limited to,media such as computer diskettes, CD ROM discs, magneto-opticalcartridges, ZIP discs, and any other physical entity bearing digitallyencoded data.

Depending upon the exact nature of such configurations, additionalcomponents, for example wires, antennas, receivers, transmitters and/ortransceivers, a telephony network and other equipment may be requiredfor communication. A portion of these additional components may alreadyexist as part of established communication networks. One ordinarilyskilled in the art will be capable of assembling such a communicationchannel 88 from commercially available components.

Charge battery supply 90 is employed in those preferred embodiments ofcontrol device 32 which include a rechargeable battery 42. It serves toapply a charge to battery 42 through charge battery block 52. Power forthis purpose and all other functions of device 34 comes from powersupply 91. Second microprocessor 84 performs all of the intelligence anddata processing functions of check device 34 and preferably includessubunit program module blocks as illustrated in FIG. 5 including: asecond control block 92, a second calculation block 94, a second set-upparameters block 98, a second pattern definition block 100, and a changeinformation block 102, as well as a second data memory 96.

Computer device 36 indicates any type of electronic device which iscapable of performing computations, including, but not limited to,personal computers (PC); Macintosh™ computers; mainframe computers;graphical workstations; handheld computing devices; or any other knownand available computational device.

Control device 32 is fixed in the mouth of a patient either for a shortterm or long term. In certain embodiments of the present inventiondevice 32 is not fixed and is held freely in the mouth and in otherembodiments control device 32 is preferably removable by the patient.For the purposes of this specification and the accompanying claims“long-term” is meant to refer to a prolonged time period of severalweeks to several months or preferably several years. For the purposes ofthis specification and the accompanying claims “short-term” is meant torefer to a shorter time period of several hours to a day or severaldays.

FIG. 6A shows control device 32 attached to a molar tooth 104 by meansof a band 106, which may take the form for example, but not limited to,an orthodontic band, orthodontic braces, a dental fixture, a hookingarrangement or other such physical structure as to affix the device tothe teeth or other oral structure as my be known in the art. In certainembodiments device 32 is fixed in the oral cavity so as to preferablystimulate the submandibular and sublingual glands. One such embodimentis illustrated in FIG. 6B. FIG. 6B illustrates fixation of controldevice 32 on the mandibular teeth 110 through use of a mouth guard 108.Mouth guard 108 is a flexible plastic frame covering the lower teeth.Mouth guard 108 is a fixture, resembling an athletic mouth guard, alsocommonly used in dental treatment, usually worn at night, especiallyafter orthodontic dental alignment, or for treatment of bruxism. Thisattachment is made so as to place the electrodes in the sublingual area112 as a non-limiting example. In other embodiments, device 32 may beimplanted within tissues with the mouth such as the gums, teeth, jawbones, palate, sublingual tissues, buccal mucosa and the like.

FIG. 10 a illustrates an alternative preferred embodiment for fixationof control device 32 within the oral cavity. FIG. 10 shows housing 38being adapted to include at least one clasp 114 for attaching controldevice 32 to at least one tooth. According to the preferred embodimentas illustrated in FIG. 10 b, control device 32 does not have to beindividually fabricated for a specific patient but rather device 32 isfabricated in a specific limited range of sizes, suitable for use inpatients with different size and shapes of oral structures. Housing 38is fabricated from a biocompatible material and seals and encases(within a body 122 of housing 38), electric utility 40 which includesbattery 42 and electronic circuitry 44 as well as at least one pair ofelectrodes 72. At least one clasp 114 is fabricated for example from anelastomeric substance, such as a flexible acrylic or other plastic, or ametal, as non-limiting examples, so as to fix onto at least one toothpreferably by an elastic, spring recoil, clamping action. Clasp 114fixes onto the at least one tooth by the pressure and friction of atleast one jaw 116 of elastic spring clasp 114 against the at least onetooth (and associated oral structures, such as the gum) to which clasp114 is applied. In configurations such as that illustrated in FIG. 10 b,with more than one jaw 116, different jaws may have different degrees ofelasticity, with one of the at least one jaws 116 being more elastic andone being more rigid. The face 120 of jaw 116 in some configurations isfitted with at least one groove 118 for conforming to indentations onthe surface of the at least one tooth to which device 32 is applied.These modifications of face 120 are done so as to increase the surfacearea of contact between face 120 and the oral structures to which device32 is fixed so as to increase the friction between the at least one jaw116 and the oral structure to which device 32 is attached. Themodifications of face 120 increase the adhesion and fixation of device32 in the oral cavity. In other embodiments, other modifications of face120 are employed to increase the surface area or the friction, such asfinger-like or tentacle-like projections, or suction cups. Still othermodifications are employed to otherwise enhance fixation such as theplacement of magnets and magnetically susceptible material in clasp 114.In applying control device 32 to the at least one tooth a lubricantsubstance can be applied or in some circumstances a temporary adhesivesubstance (similar to denture fixative) can be applied to assist inholding clasp 114 on the at least one tooth. Clasp 114 has sufficientflexibility as to be conformable to different sizes and shapes of tooth.It can be configured so as to be slidable from one tooth to another.Clasp 114 and housing 38 may be used on a mandibular or maxillary tooth,on either the right or left side of the oral cavity, and on a front orrear tooth. Preferably clasp 114 and housing 38 are adapted to fixdevice 32 onto at least one mandibular premolar or molar tooth placingelectrodes 72 against the mucosal surfaces of oral structures of thelower jaw. Housing 38 is configured so as to insure contact ofelectrodes 72 with the oral tissues. Device 32 as illustrated in FIG. 10can thus be easily attached and released and is suitable for use forshort periods of time (for example 4 to 8 hours at a time, daily) orlonger and can be made so as to be easily cleanable, and used, forexample, for two to three months before being replaced. Such a housing38 with an attachment member such as clasp 114 may find use in otherintraoral devices used for diagnostic and treatment purposes. Where morethan one intraoral device is used at a time, the housings of the devicesmay be connected to one another by a connecting member such as band orelastic. For example a band may connect two such housings on differentsides of the mouth, or an elastic may be employed to connect twohousings, one on the mandibular teeth and one on the maxillary teeth.

The stimulation sequence delivered by control device 32 typicallyinvolves emitting of a series of square wave shaped current pulses.Typically, the pulse has an intensity within the range of 10-200microamperes, preferably 60-120, most preferably 100 with each pulselasting about 5-100 millisecs, preferably 10-30, most preferably 10-20msec, with a pause between pulses of 50-1000 ms, preferably 100-500 ms,most preferably 400-600 ms. Each pulse may be either single ordual-phase polarity, preferably dual-phase polarity. The pulse numbersin each series may be from 60-600, preferably 100-400, and mostpreferably 200-300.

Each parameter may be set prior to use or use the pre-set defaultparameters. After, installation, some parameters may be set for theindividual particularly the set moisture level which is determined byrelaxation time. The electronic circuitry by which stimulating signalscan be produced and applied in the mouth according to the presentinvention is well described in the art (see, for example, U.S. Pat. Nos.4,519,400, 4,637,405, 4,244,373, and 5,188,104). It will be appreciatedthat other specific circuitry capable of performing the same functionmay occur to those skilled in the art.

The above described system for electrical stimulation of salivation willfind use primarily in conjunction with a method for electricalstimulation of salivation that can be used for the treatment ofxerostomia. Such a method for electrical stimulation of salivationincludes the steps of: (a) attaching a device for electrically detectinga measure of saliva in an oral cavity of an individual and fordelivering electrical impulses to the oral cavity of the individual soas to induce production of saliva from at least one salivary gland (suchas control device 32), device 32 having at least one pair of electrodes(72) being placed against a tissue of the oral cavity; (b) detecting aninput signal indicative of the measure of moisture within the oralcavity; (c) comparing the measure to a moisture limit value; and (d)delivering the electrical impulses based on a result of the comparing.This method for use of system 30 to treat xerostomia may be bestunderstood with reference to FIG. 7. The method for electricalstimulation of salivation making use of system 30 as disclosedhereinabove includes, as a non-limiting example, the steps of: (a) step200: setting stimulation pulse parameters. The doctor can accept thepre-set default parameters of system 30 or can change the defaultparameters and install a new set of parameters. This action is performedusing control device 34, and preferably computer device 36. (b) Step202: attaching control device 32 in the mouth of a patient, with theelectrodes thereof in close proximity to the salivary glands. (c) Step204: Executing stimulation program 206.

The further steps of stimulation program 206 are illustrated in the flowchart of FIG. 8. The method of stimulation program 206 further comprisesthe steps of: (1) 208: Checking battery quality. If battery quality isgood, proceed to step 209, if not change or charge battery. (2) 209:Checking for connection of control device 32 with check device 34. Ifconnected, exchange information between devices 32 and 34. If noconnection, proceed to: (3) 210: Checking contact quality. If nocontact, return to 208. (4) 212: Emitting a measuring pulse andmeasuring parameters of the state of the salivary gland (e.g.,resistance, capacity, relaxation time). (5) 214: Emitting a salivationinducing series of pulses in accordance with set-up parameters. (6) 216:Recording parameters to temporary memory. (7) 218: Counting number ofpulses (8) 220: Repeating from step 206 until the number of pulsesequals the installed parameter of number of pulses to deliver (9) 222:Estimating trend data and analyze. (224) Deciding on emitting furtherpulses. If trend derivative >0, continue with emitting pulses byreturning to step 208. If trend derivative is =0, set up new parameters.This may be performed, as a non-limiting example, by microprocessor 46,where control block 62 interacts with current reference 50 to change thecurrent level (e.g., from 50 to 150 microamperes as a non-limitingexample) or changes the cycle timing parameters (e.g., changing thetiming of the pulse emission or pause time as non-limiting examples.) Iftrend derivative>a border 1 (114) (which can be either a pre-set, orentered parameter, such as a 1 second relaxation time difference betweenmeasurements as a non-limiting example), stop emitting pulses and afterdelay 2 [116] (which can be either a pre-set, or entered parameter, suchas 5-30 minutes as a non-limiting example), return to step 208. The flowchart of FIG. 8 shows these steps in somewhat greater detail.

The flow charts of FIG. 12-14 illustrate alternate algorithms asnon-limiting examples of methods of use of control device 32 and system30 for delivering a stimulus only (FIG. 12), measuring only (FIG. 13),and stimulus and measuring (FIG. 14). The algorithm of FIG. 14 iscapable of incorporating adaptation and “learning”.

Further specifically envisaged as being within the scope of the presentinvention are alternate applications of this system and method forelectrical stimulation of secretion of other body tissues, such as otherexocrine glands—for example, but limited to, the lacrimal gland, whichis also involved in other sicca syndromes such as Sjogren's syndrome(presenting with dry eyes), or the mammary gland. Also specificallyenvisaged as being within the scope of the present invention arealternate applications of this system and method in non-human species.

The present invention successfully addresses the shortcomings of thepresently known configurations by providing a system and a method ofusing same for electrically detecting a lack of saliva in the oralcavity and for electrically stimulating the oral cavity so as to inducethe production of saliva from the salivary glands.

Additional objects, advantages, and novel features of the presentinvention will become apparent to one ordinarily skilled in the art uponexamination of the example hereinbelow, which is not intended to belimiting. Additionally, each of the various embodiments and aspects ofthe present invention as delineated hereinabove and as claimed in theclaims section below finds experimental support in the example describedhereinbelow.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims.

All publications, patents and patent applications mentioned in thisspecification are herein incorporated in their entirety by referenceinto the specification, to the same extent as if each individualpublication, patent or patent application was specifically andindividually indicated to be incorporated herein by reference. Inaddition, citation or identification of any reference in thisapplication shall not be construed as an admission that such referenceis available as prior art to the present invention.

EXAMPLE

Reference is now made to the following example, which together with theabove descriptions, illustrate the invention in a non limiting fashion.

Preliminary tests have been conducted to test the relation betweenrelaxation time, as defined hereinabove, and “mouth moisture.” Salivawas measured by standard “whole saliva” procedures. The steps of theexperiment were as follows: (1) Measure relaxation time, (2) Measurewhole saliva (3 minutes), (3) Administer stimulus for 5 minutes toincrease salivation (60 μA, 100 μA, 300 μA, 500 μA), (4) Measure wholesaliva (3 minutes), and (5) Measure relaxation time.

The data is based on 44 tests with 13 subjects. The results (FIG. 9A)showed that relaxation time was directly related to saliva quantity for11 of the 13 subjects. Higher relaxation times reflected increasedsaliva. The average gradient was approximately 2.5 sec/g saliva. The twosubjects with deviant results were “very dry”. The dotted lines in thegraph represent tests performed after drinking water.

A detailed analysis of repeated measurements was done for one subject asshown graphically in FIG. 9B. Higher relaxation time was related toincreased saliva in 16 of the 18 measurements. The gradient rangedbetween 1.8 and 6 sec/g saliva with a mean of 2.5 sec/g saliva.

1. A system for electrically detecting a lack of saliva in an oralcavity of an individual and for electrically stimulating the oralcavity, so as to induce production of saliva from at least one salivarygland, said system comprising: a control device for detecting a measureof salivation in the individual and for delivering electrical impulsesto the oral cavity of the individual, said control device having atleast one pair of electrodes provide a contact with a tissue of the oralcavity; a check device for obtaining the data of said measure ofsalivation and for modifying at least one parameter of said controldevice, and a computer device for exchanging information with said checkdevice; wherein said measure of salivation is a relaxation time, saidrelaxation time being a measure of time required for a voltagedifference between said at least one pair of electrodes to reach apredetermined level of an initial value of said voltage difference aftera measuring pulse is applied.
 2. The system as in claim 1, wherein saidpredetermined level is selected from the group consisting of 40% and50%.
 3. A device for electrically detecting a measure of saliva in anoral cavity of an individual and for delivering electrical impulses tothe oral cavity of the individual so as to induce production of salivafrom at least one salivary gland, said device comprising: a hermeticallysealed housing fixable within the oral cavity; an electrical utilityenclosed within said housing for detecting an input signal for detectionof the measure of salivation and for generating the electrical impulses,said electrical utility including a power source and a signal generator,and at least one pair of electrodes electrically coupled to saidelectrical utility, wherein said at least one pair of electrodes providea contact with a tissue of the oral cavity; wherein said measure ofsalivation is a relaxation time, said relaxation time being a measure oftime required for a voltage difference between said at least one pair ofelectrodes to reach a predetermined level of an initial value of saidvoltage difference after a measuring pulse is applied.
 4. The device asin claim 3, wherein said predetermined level is selected from the groupconsisting of 40% and 50%.
 5. A method for electrical stimulation ofsalivation comprising the steps of: attaching a device for electricallydetecting a measure of saliva in an oral cavity of an individual and fordelivering electrical impulses to said oral cavity of said individual soas to induce production of saliva from at least one salivary gland, saiddevice having at least one pair of electrodes, said electrodes beingplaced against a tissue of said oral cavity; detecting an input signalindicative of said measure of moisture within said oral cavity;comparing said measure to a moisture limit value, and delivering saidelectrical impulses based on a result of said comparing; wherein saidmeasure of salivation is a relaxation time, said relaxation time being ameasure of time required for a voltage difference between said at leastone pair of electrodes to reach a predetermined level of an initialvalue of said voltage difference after a measuring pulse is applied.